Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of transformation by Rous sarcoma virus on the ornithine decarboxylase levels of chick embryo fibroblasts was studied. Infection with Rous sarcoma virus resulted in increased ornithine decarboxylase activity which preceded morphological alterations by at least 24 hr. The ornithine decarboxylase levels of normal controls, unlike those in Rous sarcoma virus-infected cells, declined with age, so that the enzyme activity of transformed cells was increased twentyfold 5 days postinfection. Infection with a temperature-sensitive mutant of Rous sarcoma virus, T5, stimulated ornithine decarboxylase activity of chick embryo fibroblasts at the permissive (37 degrees) but not at the nonpermissive (42 degrees) temperature. The ornithine decarboxylase activity of T5-infected cells shifted from 42 degrees to 37 degrees increased within 2 hr and reached the levels of wild-type, Schmidt-Ruppin-17A-transformed cells in 11 hr. When T5-transformed fibroblasts were shifted to the nonpermissive temperature, ornithine decarboxylase activity decreased fivefold within 4 hr and paralleled the levels of normal controls in 11 hr. Shifting of temperatures of incubation caused comparable alterations in cellular putrescine but not in spermine or spermidine content.
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PMID:Polyamine metabolism in normal and in virus-transformed chick embryo fibroblasts. 17 29

The stimulation of quiescent murine fibroblasts by growth factors and by phorbol esters results in a rapid and transient transcriptional activation of a large group of so-called immediate early genes. Several such genes were found to be induced in chicken embryo fibroblasts following activation of a temperature sensitive (ts) Rous sarcoma virus v-src mutant following temperature shift (Simmons et al., 1989). In contrast, the classical immediate early genes c-myc, c-fos and c-jun were essentially uninducible upon activation of a ts v-src mutant in rat-1 fibroblasts (Welham et al., 1990). We have cloned 9 cDNAs of genes that are rapidly and transiently inducible in rat fibroblasts by ts v-src mutants, and by a ts Fujinami sarcoma virus v-fps mutant. Six of these cDNAs are derived from the known immediate early genes NGFI-A, KC, c-fos, tissue factor, PC4 and ornithine decarboxylase; the other three cDNAs have not been described before. These 9 genes showed individual profiles of inducibility by fetal calf serum, epidermal growth factor (EGF) and by phorbol esters. Their response to the retroviral oncogenic protein-tyrosine kinases correlated best with the one to EGF, suggesting a common pathway of signal transduction. c-fos did not respond strongly to this pathway but was well induced by fetal calf serum. NGFI-A, however, was induced to a similar extent by all activators tested. Furthermore, we demonstrated that the induction of several of these genes by the retroviral oncogenic protein-tyrosine kinases is rapid, direct and occurs at the transcriptional level.
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PMID:The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes. 186 68

We used molecular cloning to isolate a functional gene for mouse ornithine decarboxylase (OrnDCase; L-ornithine carboxy-lyase, EC 4.1.1.17) from a cell line in which that gene had been selectively amplified. The position of the 5' terminus of the mRNA was identified, and the coding sequence was shown to be preceded by a 312- or 313-nucleotide (nt) untranslated leader. The latter is highly G + C rich, particularly in its 5'-most portion. The leader can be anticipated to have extensive and stable secondary structure. The transcription unit of the gene is of relatively small size, approximately equal to 6.2 kilobases (kb) from the start site to the proximal site of polyadenylylation. Sequence analysis of DNA near the transcription start position demonstrated the presence of a "TATA" box, but no "CAAT" box. Functional properties of the cloned gene were tested by transfecting it into cultured cells. Expression of the putative full-length gene efficiently conferred ornithine decarboxylase activity on recipient mutant cells deficient in that activity. To assess the function and strength of the OrnDCase promoter region and to delimit its boundaries, we used a transient expression assay. Upstream of a bacterial chloramphenicol acetyltransferase gene was placed a portion of the OrnDCase gene, including the presumed promoter region, spanning a region from approximately equal to 3.0 kb 5' of the site of transcription initiation to the first 250 nt of the transcript. When expressed in mouse NIH 3T3 cells, this OrnDCase genomic element was comparable in strength to the Rous sarcoma virus long terminal repeat promoter. A similar construct, truncated so as to retain only 264 base pairs of the OrnDCase gene 5' to the site of transcription start, yielded undiminished levels of expression.
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PMID:Mouse ornithine decarboxylase gene: cloning, structure, and expression. 335 75

When monolayer Chinese hamster cells are treated with trypsin for short periods of time, ornithine decarboxylase (ODCase) activity increases two- to fourfold. This increase can be blocked by aprotinin, a protease inhibitor, and is not observed when cultures are dislodged from substrate mechanically prior to contact with exogenous trypsin. The trypsin-induced increase in ornithine decarboxylase activity is not due to degradation of enzyme or inhibitor molecules or to new enzyme synthesis. Immunoprecipitable protein, radiolabeled with [3H]alpha-difluoromethylornithine in vitro, is the same molecular weight in cells harvested with or without trypsin. Protein-bound levels of this specific enzyme-activated irreversible inhibitor of ornithine decarboxylase are unchanged by trypsin treatments that increase enzyme activity. Trypsin treatment of rat embryonic fibroblasts, transformed by a temperature-sensitive mutant of Rous sarcoma virus, increases ODCase activity in cells growing at the nonpermissive, but not at the permissive, temperature for the transformed phenotype. These results suggest that ornithine decarboxylase can be activated by exogenous trypsin treatment in a manner that is dependent on cell adhesion properties, which are modified in transformed cells.
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PMID:Activation of ornithine decarboxylase in monolayer cells treated with trypsin. 384 Aug 6

Ornithine decarboxylase (ODC) induction during G1 phase of the cell cycle was compared in Rat-1 fibroblasts and in Rat-1 fibroblasts transformed by the B77 wild-type Rous sarcoma virus (RSV) and by the thermosensitive mutant LA24/RSV. In Rat-1 cells, maximal enzyme activity detectable at mid G1 declined to basal levels by G1-S. The ODC increase was inhibited by actinomycin D and cycloheximide and was dependent on the addition of serum growth factors. Rat-1 (B77 wild-type RSV) cells expressed a greater amount of enzyme activity after serum stimulation, and the maximal level of enzyme activity detectable at mid G1 declined only 50% so that elevated ODC was maintained during G1-S transition. The enzyme increase in the transformed cell line was not dependent on serum growth factors. Fresh medium addition alone induced enzyme activity. Induction in the presence or absence of serum required both RNA and protein synthesis. ODC induction in the transformed cells was less sensitive to repression by exogenous putrescine addition. A 100-fold greater concentration of the diamine was required to produce comparable inhibition in the Rat-1 (B77 wild-type RSV) as compared to the Rat-1 cell. These alterations in the characteristics of ODC expression were found to be a consequence of the transforming function of RSV in the Rat-1 cell line transformed by the thermosensitive viral mutant LA24. In response to serum stimulation at the nonpermissive temperature (39 degrees), Rat-1 (thermosensitive mutant LA24/RSV) cells displayed a discrete G1-phase ODC induction while those cells maintained at the permissive temperature (35 degrees) exhibited a greater and prolonged ODC induction in G1 and S phases. A shift from 39 to 35 degrees in the absence of any medium or serum addition stimulated the induction of ODC expressed in a transformed phenotypic manner. Greater concentrations of exogenous putrescine were required to repress the induction of ODC at 35 than at 39 degrees. Alterations in ODC regulation, therefore, may be inherent to the neoplastic phenotypic change.
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PMID:Ornithine decarboxylase induction during B1 progression of normal and Rous sarcoma virus-transformed cells. 625 84

Tertiary cultures of chick embryo fibroblasts infected and transformed by the wild-type Rous sarcoma virus, when actively growing at 35 degrees C, had higher putrescine levels than the respective uninfected cells. Transformed cells also had much higher specific activity of ornithine decarboxylase (EC 4.1.1.17) than the normal fibroblasts. At 41 degrees C the difference in putrescine levels between the normal and the transformed cells was less marked, and both cell types showed a relative accumulation of spermine. Cultures infected with the NY68 mutant virus, which is temperature-sensitive for transformation, showed at 41 degrees C normal cell morphology and intermediate polyamine patterns, while at 35 degrees C a transformed phenotype was found in both aspects. In shift-down experiments a change towards the permissive temperature pattern of polyamine metabolism was evident within 2-3 h. Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase efficiently reduced the enzyme activity as well as the levels of both putrescine and spermidine in all culture types and temperatures. Incubation of Rous sarcoma virus-transformed cells with 3 mM difluoromethylornithine for 36 h did not affect the maintenance of the transformed state. Likewise, when NY68-infected cultures were exposed to difluoromethylornithine at 41 degrees C for 12 h and then shifted down to 35 degrees C, the appearance of the transformed morphology took place concomitantly with that of the control cultures without respective changes in the polyamine levels. This suggests that the transformation-associated pattern of polyamines in chick embryo fibroblasts is not a prerequisite for morphological transformation of these cells.
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PMID:Temperature-dependent and transformation-associated changes in polyamine metabolism in normal and Rous sarcoma virus-infected chick embryo fibroblasts. 627 Dec 45

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, becomes upregulated during cell proliferation and transformation. Here we show that intact ODC activity is needed for the acquisition of a transformed phenotype in rat 2R cells infected with a temperature-sensitive mutant of Rous sarcoma virus. Addition of the ODC inhibitor alpha-difluoromethyl ornithine (DFMO) to the cells (in polyamine-free medium) before shift to permissive temperature prevented the depolymerization of filamentous actin and morphological transformation. Polyamine supplementation restored the transforming potential of pp60v-src. DFMO did not interfere with the expression of pp60v-src or its in vitro tyrosine kinase activity. The tyrosine phosphorylation of most cellular proteins, including ras GAP, did not either display clear temperature- or DFMO-sensitive changes. A marked increase was, however, observed in the tyrosine phosphorylation of phosphatidylinositol 3-kinase and proteins of 33 and 36 kD upon the temperature shift, and these hyperphosphorylations were partially inhibited by DFMO. A DFMO-sensitive increase was also found in the total phosphorylation of calpactins I and II. The well-documented association of GAP with the phosphotyrosine-containing proteins p190 and p62 did not correlate with transformation, but a novel 42-kD tyrosine phosphorylated protein was complexed with GAP in a polyamine- and transformation-dependent manner. Further, tyrosine phosphorylated proteins of 130, 80/85, and 36 kD were found to coimmunoprecipitate with pp60v-src in a transformation-related manner. Altogether, this model offers a tool for sorting out the protein phosphorylations and associations critical for the transformed phenotype triggered by pp60v-src, and implicates a pivotal role for polyamines in cell transformation.
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PMID:Polyamines are essential for cell transformation by pp60v-src: delineation of molecular events relevant for the transformed phenotype. 768 51